Combination of hyperhomocysteinemia and ischemic tolerance in experimental model of global ischemia in rats

Area of Science:

• Neuroscience
• Biochemistry
• Pathology

Background:

• Mild-to-moderate hyperhomocysteinemia (hHcy) is linked to increased cerebrovascular disease risk.
• Hyperhomocysteinemia is a known risk factor for brain ischemia.
• The interplay between hHcy, ischemic preconditioning (IPC), and ischemia-induced neurodegeneration is not fully understood.

Purpose of the Study:

• To investigate the effects of hHcy alone and in combination with IPC on ischemia-induced neurodegeneration in rat brains.
• To analyze the impact of hHcy and IPC on MAPK/p-ERK1/2 and MAPK/p-p38 expression following brain ischemia.
• To elucidate the role of MAPK signaling pathways in the context of hHcy and ischemic brain injury.

Main Methods:

• Hyperhomocysteinemia (hHcy) was induced in rats via homocysteine administration.
• Ischemic preconditioning (IPC) was applied, followed by global forebrain ischemia (four-vessel occlusion).
• Neurodegeneration was assessed using Fluoro-Jade C and TUNEL staining; MAPK signaling was analyzed via Western blot and immunohistochemistry.

Main Results:

• hHcy alone significantly increased neurodegeneration in the hippocampus and cortex.
• hHcy altered MAPK signaling, elevating p-ERK and decreasing p-p38 levels post-ischemia.
• IPC, even in the presence of hHcy, demonstrated a neuroprotective effect against lethal ischemic damage.

Conclusions:

• IPC can preserve neuronal tissue from severe ischemic injury, even in rats with hyperhomocysteinemia.
• ERK and p38 MAPK signaling pathways are tightly integrated and play crucial roles in responding to hHcy and brain ischemia/IPC challenges.
• This study highlights the potential of IPC as a therapeutic strategy for ischemic brain injury, particularly in individuals with elevated homocysteine levels.